P493 - EXPLORING THE RELATIONSHIP BETWEEN URINE SODIUM LEVELS AND RESPONSE TO GLEPAGLUTIDE TREATMENT IN SHORT-BOWEL SYNDROME WITH INTESTINAL FAILURE

P493

EXPLORING THE RELATIONSHIP BETWEEN URINE SODIUM LEVELS AND RESPONSE TO GLEPAGLUTIDE TREATMENT IN SHORT-BOWEL SYNDROME WITH INTESTINAL FAILURE

R. H. Foerster^1,*, T. S. Nielsen², M. Berner-Hansen^2,3, G. Lamprecht¹

¹Department of Gastroenterology and Endocrinology, University Medical Center, Rostock, Germany, ²Zealand Pharma, Søborg, ³Digestive Disease Center, Bispebjerg University, Copenhagen, Denmark

Rationale: Glepaglutide, a long-acting glucagon-like peptide 2 (GLP-2) analogue, reduces need for parenteral support (PS) and increases nutrient absorption including sodium, in patients with short-bowel syndrome (SBS). We retrospectively studied the association between urine sodium levels and PS changes in response to glepaglutide for SBS intestinal failure (SBS-IF) patients.

Methods: The phase 3a EASE SBS-1 trial randomized 106 SBS-IF patients to receive glepaglutide 10 mg once or twice weekly vs. placebo for 24 weeks. All were included in this subgroup analysis. We defined sodium depletion as sodium concentration <20 mmol/l or sodium/potassium ratio <1 in spot urine at baseline. The following analyses were performed post hoc: first, ANCOVA for the change in PS volume from baseline to week 24 (primary endpoint EASE SBS-1); second, a logistic regression model for achieving predefined key secondary endpoint of clinical response (>=20% reduction in PS volume from baseline to weeks 20 and 24). We adjusted for sodium depletion, colon-in-continuity (CiC), treatment (active/placebo), and treatment-by-sodium depletion interaction.

Results: Mean age 55y, 54% women, 51% CiC, 14.4±7.8 L/week baseline PS volume. 42% (22/52) of patients without CiC vs. 9% (5/54) with CiC were sodium depleted at baseline (p<0.0001). Patients without sodium depletion (n=79) had a significantly greater PS reduction with glepaglutide vs. placebo (p=0.02). The nondepleted patients receiving glepaglutide were numerically more likely to achieve a clinical response (p=0.12). Patients with sodium depletion (n=27) had an insignificant difference in PS reduction or clinical response.

Conclusion: Sodium depletion is more common in SBS-IF without CiC. Further research into how the restoration of sodium balance affects the efficacy of glepaglutide may allow more patients to benefit.

Disclosure of Interest: None declared